Table 7.
Comparisons of study features investigating DNA methylation across the genome of ME/CFS patients compared to controls
| Study | Tissue | Method | Cohort | Diagnostic criteria | Statistical thresholds | No. of significant differences |
|---|---|---|---|---|---|---|
| NZ | PBMCs | Reduced representation bisulphite sequencing |
P = 10 5 females 5 males C = 10 5 females 5 males |
Canadian criteria |
DMAP ANOVA F test Raw P < 0.05, methylation diff ± 15% MethylKit Fisher’s exact test FDR corrected P < 0.05. methylation diff ± 15% |
DMAP: 76 (52% hypo-methylated) Methylkit: 394 (56% hypo-methylated) |
| A | CD4 + T cells | Infinium HumanMethylation450 BeadChip |
P = 25 21 females 4 males C = 18 10 females 8 males |
Fukuda criteria | Raw P value < 0.05, methylation fold change > 2.0 | 120 (85% hypo-methylated) |
| B | PBMCs | Infinium HumanMethylation450 BeadChip |
P = 12, C = 12 All female |
Fukuda and Canadian criteria | Wilcoxon-rank sum test P < 0.05, FDR corrected P < 0.05 (Benjamini-Hochberg). Mean beta difference > 0.20 | 1192 (72% hyper-methylated) |
| C | PBMCs | Infinium HumanMethylation450 BeadChip |
P = 49, C = 25 All female |
Fukuda and Canadian criteria | Wilcoxon-rank sum test P < 0.05, FDR corrected P < 0.05. Mean beta difference > 0.05 | 12,608 (71.6% hyper-methylated) |
| D* | PBMCs | Illumina Methylation EPIC microarray |
P = 13, C = 12 All female |
Fukuda and Canadian criteria | FDR-corrected P value < 0.05 absolute beta difference > 0.05 | 17,296 (98% hypo-methylated) |
| E | CD3 + T Cells | Infinium HumanMethylation450 BeadChip |
P = 43 34 females 9 males C = 36 27 females 9 males) |
Fukuda and Canadian criteria | P value < 0.05 permutation analysis, mean percentage methylation difference > 5% | 133 (74% hyper-methylated) |
A table comparing the NZ study with the five previous studies investigating DNA methylation in ME/CFS patients vs. controls. (NZ = this study, A = Brenu et al. 2014 [6], B = de Vega et al. 2014 [7], C = de Vega et al. 2017 [8], D = Trivedi et al. 2018 [9], E = Herrera et al. 2018 [10]) The table includes the cell type utilised, the method used in the analysis, the numbers and gender included in the cohort, diagnostic criteria of the patients and the statistical thresholds utilised in the analyses. *D (Trivedi et al. [9]) included a larger cohort for pyrosequencing validation with a total of 33 cases and 31 controls from three geographical locations